Dr. Abigail Ruiz

Institution: UPR – Ponce Campus

Email: abigail.ruiz@upr.edu

In vivo efficacy of the CXCR4 inhibitor AMD3100 in the rat model of endometriosis

Endometriosis is a chronic and recurrent disease that may affect up to 50% of women with pelvic pain and subfertility, affecting the quality of life of approximately 10% of women during their reproductive ages. Endometriosis increases the risks for the development of other diseases including, ovarian cyst, uterine fibroids, pelvic inflammatory disorder, interstitial cystitis, irritable bowel syndrome, constipation/dyschezia, ovarian cancer, and endometrial cancer. The G Protein Coupled Receptor, CXCR4, expression is elevated in endometriosis. This G Protein coupled receptor is activated by its specific ligand, CXCL12. The CXCR4- CXCL12 axis roles include proliferation, migration, invasion, angiogenesis, and chemotaxis, all of which are of relevance for the endometriosis phenotype. In addition, CXCR4 is associated with autophagy initiation and regulation. We and others have demonstrated an increase in CXCR4 and autophagy marker expression in endometriosis lesions from human samples and in an animal model. We reported a decrease in migration and invasion in endometriotic cells treated with AMD3100 in combination with the ligand CXCL12. Based on this evidence, additional studies are necessary to identify the potential effect of AMD3100 blocking the CXCR4-CXCL12 axis leading to a reduction in endometriotic lesion development, by a decrease in autophagy and in the immune response leading to less cell survival in an in vivo model. We hypothesize that AMD3100 will decrease inflammation mediated by CXCR4 in the peritoneal cavity of the rat model of endometriosis leading to a decrease in lesion numbers, size, and apoptosis mediated by autophagy. The goals of the pilot proposal are to determine the effect of AMD3100 treatment reducing endometriosis lesions development and its effects at the molecular level using an in vivo model of endometriosis in rats. Studies are necessary to identify new non-hormonal candidate treatments for this incapacitating disease using in vivo endometriosis animal models through preclinical investigations.